Experimental AAV-Tyrosinase Based Anti-Melanoma Vaccine

Sep 18, 2019

Study Objective
The purpose of this trial is to evaluate the safety and preliminary efficacy of a novel vaccine in companion dogs diagnosed with oral melanoma. A tumor-specific antigen (tyrosinase) carried by a FDA-approved bioengineered viral vector (AdenoAssociated Virus; AAV) is injected intramuscularly into the quadriceps muscle of the rear leg. Dogs will be vaccinated once with the AAV-Tyrosinase vaccine in a 3 x 3 dose escalation trial. The first cohort will be treated with a starting dose that is considered to be safe based on extrapolation from animal toxicological data, and the subsequent cohorts are treated at increasing dose levels. If none of the three patients in a cohort experiences a dose-limiting toxicity, another three patients will be treated at the next higher dose level. However, if one of the first three patients experiences a dose-limiting toxicity, three more patients will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three patients experience dose-limiting toxicities (ie, ≥33% of patients with a dose-limiting toxicity at that dose level). Preliminary data on mice suggest activation of both a cytotoxic CD8+ T-cells and a humoral response either directly or by a cross-presentation pathway against the tumor. Safety of AAV vectors have been tested in humans and dogs. In addition, the tyrosinase antigen is currently used as a target for an anti-cancer vaccine in humans and dogs.

Eligibility Requirements
The requirements for participating in the trial are as follows:
• Any dog, male or female, with histologic or cytological confirmed oral melanoma with at least stage 1
(the WHO staging scheme for dogs with oral melanoma is based on size, with stage I = <2-cm-diameter tumor, stage II = 2- to <4-cm-diameter tumor, stage III = > or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis);
• Dogs over 5 kg
• Pre-enrollment requirements: CBC, chemistry panel, radiographs, +/- abdominal U/S
• No steroid use within 7 days of enrollment
• No concurrent illness
• Performance score of 0 or 1
• Dogs with expected survival time of over 6 weeks

Exclusion Criteria
The following criteria will be used for excluding participation in the trial:
• Dogs less than 5kg
• Steroid use within 7 days of enrollment
• Prior ONCEPT therapy
• Clinical findings precluding use of vaccine
• Pre-existing antibodies to AAV as evaluated by laboratory analysis
• Liver values (ALT, AST) > 2 x ULN

Post AAV-Injection Monitoring
Dogs in the trial will be evaluated in pre-enrollment screening visit, during treatment, and after treatment monitoring. All animals will be followed up every 3-6 months after the last visit to assess general heath and survival. The dogs enrolled in the trial will be monitored as follows:
• Evaluating lymph nodes, lungs, and chest radiographs, respectively
• Blood samples and urinalysis on each visit
• Evaluating vaccine-specific immune response
• Liver values (ALT, AST) > 2 x ULN